Synthetic programs are continuing to develop new ligands for imaging brain drug receptors by positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanning, and the NIH Opiate Total Synthesis is employed to provide previously inaccessible unnatural enantiomers of opiates and derivatives. The binding characteristics, pharmacology, immunochemistry, and the multiplicity of opioid receptors were examined, and new drugs were explored as treatment agents for cocaine abuse and for their interaction with the dopamine transporter. Multiple delta opioid receptors - Ligand binding data, utilized to determine whether subtypes of the delta opioid receptor existed in rat brain membranes, supported pharmacological studies demonstrating delta receptor subtypes which mediate antinociception. Immunoregulatory opioids - Opioid compounds, such as morphine and beta- endorphin, are active immunoregulatory molecules in vitro and in vivo, and opioid receptors are present on immune cells. We found that the lymphocyte mu-class binding site has a molecular eight of 58 kDa under nonreducing conditions and 70 kDa under reducing conditions, compared with brain mu- class binding sites which were found to have a molecular weight of 54 kDa under nonreducing conditions. These and other data indicate the presence of a functional m-type opioid receptor on cells of the immune system and add to the concept of bidirectional circuitry between the immune and neuroendocrine systems. Potential treatment agents for cocaine abuse - The high affinity dopamine reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3- phenylpropyl]piperazine (GBR 12909) produced a dose-dependent decrease in the binding of [3H] cocaine or [3H]GBR 12935 to the dopamine transporter. GBR 12909 antagonizes the ability of cocaine to elevate extracellular dopamine by 50%. Further studies will be needed to evaluate a possible role for GBR 12909 in the medical treatment of cocaine addiction.